Assessment of Postnatal Corticosteroids for the Prevention of Bronchopulmonary Dysplasia in Preterm Neonates A Systematic Review and Network Meta-analysis

IMPORTANCE The safety of postnatal corticosteroids used for prevention of bronchopulmonary dysplasia (BPD) in preterm neonates is a controversial matter, and a risk-benefit balance needs to be struck. OBJECTIVE To evaluate 14 corticosteroid regimens used to prevent BPD: moderately earlyinitiated, lowcumulative dose of systemic dexamethasone (MoLdDX); moderately early-initiated, medium cumulative dose of systemic dexamethasone(MoMdDX); moderately early-initiated, high cumulative dose of systemic dexamethasone (MoHdDX); late-initiated, lowcumulative dose of systemic dexamethasone (LaLdDX); late-initiated, medium cumulative dose of systemic dexamethasone (LaMdDX); late-initiated, high cumulative dose of systemic dexamethasone (LaHdDX); early-initiated systemic hydrocortisone (EHC); late-initiated systemic hydrocortisone (LHC); early-initiated inhaled budesonide (EIBUD); early-initiated inhaled beclomethasone (EIBEC); early-initiated inhaled fluticasone (EIFLUT); late-initiated inhaled budesonide (LIBUD); late-initiated inhaled beclomethasone (LIBEC); and intratracheal budesonide (ITBUD). DATA SOURCES PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, World Health Organization's International Clinical Trials Registry Platform (ICTRP), and CINAHL were searched from inception through August 25, 2020. STUDY SELECTION In this systematic review and network meta-analysis, the randomized clinical trials selected included preterm neonates with a gestational age of 32 weeks or younger and for whom a corticosteroid regimen was initiated within 4 weeks of postnatal age. Peer-reviewed articles and abstracts in all languages were included. DATA EXTRACTION AND SYNTHESIS Two independent authors extracted data in duplicate. Network meta-analysis used a bayesian model. MAIN OUTCOMES AND MEASURES Primary combined outcomewas BPD, defined as oxygen requirement at 36 weeks' postmenstrual age (PMA), or mortality at 36 weeks' PMA. The secondary outcomes included 15 safety outcomes. RESULTS Atotal of 62 studies involving 5559 neonates (mean [SD] gestational age, 26 [1] weeks) were included. Several regimenswere associated with a decreased risk ofBPDor mortality, includingEHC(risk ratio [RR], 0.82; 95% credible interval [CrI], 0.68-0.97); EIFLUT(RR, 0.75; 95% CrI, 0.55-0.98); LaHdDX(RR, 0.70; 95% CrI, 0.54-0.87); MoHdDX(RR, 0.64; 95% CrI, 0.48-0.82); ITBUD (RR, 0.73; 95% CrI, 0.57-0.91); andMoMdDX(RR, 0.61; 95% CrI, 0.45-0.79). Surface under the cumulative ranking curve (SUCRA) value ranking showed thatMoMdDX (SUCRA, 0.91), MoHdDX(SUCRA, 0.86), and LaHdDX(SUCRA, 0.76) were the 3 most beneficial interventions. ITBUD (RR, 4.36; 95% CrI, 1.04-12.90); LaHdDX(RR, 11.91; 95% CrI, 1.64-44.49); LaLdDX(RR, 6.33; 95% CrI, 1.62-18.56); MoHdDX(RR, 4.96; 95% CrI, 1.14-14.75); andMoMdDX (RR, 3.16; 95% CrI, 1.35-6.82) were associated with more successful extubation from invasive mechanical ventilation. EHCwas associated with a higher risk of gastrointestinal perforation (RR, 2.77; 95% CrI, 1.09-9.32). MoMdDXshowed a higher risk of hypertension (RR, 3.96; 95% CrI, 1.1030.91). MoHdDXhad a higher risk of hypertrophic cardiomyopathy (RR, 5.94; 95% CrI, 1.95-18.11). CONCLUSIONS AND RELEVANCE This study suggested that MoMdDXmay be the most appropriate postnatal corticosteroid regimen for preventing BPD or mortality at a PMA of 36 weeks, albeit with a risk of hypertension. The quality of evidence was low.

Automated summary

The study evaluated 14 corticosteroid regimens for preventing bronchopulmonary dysplasia in preterm neonates, finding that early-initiated dexamethasone and fluticasone may reduce the risk of BPD or mortality.